Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rockville, MD, 20850, USA.
BMC Cancer. 2022 May 7;22(1):512. doi: 10.1186/s12885-022-09580-7.
Indian natural products have been anecdotally used for cancer treatment but with limited efficacy. To better understand their mechanism, we examined the publicly available data for the activity of Indian natural products in the NCI-60 cell line panel.
We examined associations of molecular genomic features in the well-characterized NCI-60 cancer cell line panel with in vitro response to treatment with 75 compounds derived from Indian plant-based natural products. We analyzed expression measures for annotated transcripts, lncRNAs, and miRNAs, and protein-changing single nucleotide variants in cancer-related genes. We also examined the similarities between cancer cell line response to Indian natural products and response to reference anti-tumor compounds recorded in a U.S. National Cancer Institute (NCI) Developmental Therapeutics Program database.
Hierarchical clustering based on cell line response measures identified clustering of Phyllanthus and cucurbitacin products with known anti-tumor agents with anti-mitotic mechanisms of action. Curcumin and curcuminoids mostly clustered together. We found associations of response to Indian natural products with expression of multiple genes, notably including SLC7A11 involved in solute transport and ATAD3A and ATAD3B encoding mitochondrial ATPase proteins, as well as significant associations with functional single nucleotide variants, including BRAF V600E.
These findings suggest potential mechanisms of action and novel associations of in vitro response with gene expression and some cancer-related mutations that increase our understanding of these Indian natural products.
印度天然产物在癌症治疗中被传闻使用，但疗效有限。为了更好地了解它们的作用机制，我们检查了公开可用的 NCI-60 细胞系面板中印度天然产物活性的数据。
我们检查了在 NCI-60 癌细胞系面板中经过充分特征描述的分子基因组特征与 75 种源自印度植物天然产物的化合物在体外治疗反应之间的关联。我们分析了注释转录本、lncRNAs 和 miRNAs 的表达度量值，以及癌症相关基因中的蛋白改变单核苷酸变异。我们还检查了癌症细胞系对印度天然产物的反应与美国国立癌症研究所 (NCI) 发育治疗计划数据库中记录的参考抗肿瘤化合物反应之间的相似性。
基于细胞系反应测量的层次聚类确定了 Phyllanthus 和 cucurbitacin 产物与具有抗有丝分裂作用机制的已知抗肿瘤药物的聚类。姜黄素和姜黄素类化合物大多聚集在一起。我们发现对印度天然产物的反应与多个基因的表达有关，特别是涉及溶质转运的 SLC7A11 和编码线粒体 ATP 酶蛋白的 ATAD3A 和 ATAD3B，以及与功能单核苷酸变异的显著关联，包括 BRAF V600E。
这些发现表明了这些印度天然产物的潜在作用机制和体外反应与基因表达和一些与癌症相关的突变之间的新关联，增加了我们对这些印度天然产物的理解。
